Process for sealing capsules



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Patented Jan. 1, 1963 iifice 3,071,513 PROCESS FOR SEALING CAPSULESHerman R. De Boer, Comstock Township, Kalamazoo County, Thurlow E. King,Pavilion Township, Kalamazoo County, and Edwin L. Knoechel, KalamazooTownship, Kalamazoo County, Mich., assignors to The Upjohn Company,Kalamazoo, Mich., a corporation of Delaware No Drawing. Filed Nov. 23,1959, Ser, No. 854,566

17 Claims. (Cl. 167-83) This invention relates to a method of sealingfilled hard gelatin capsules.

A hard gelatin capsule consists of two cylinders of gelatin each ofwhich is open at one end and closed at the other end by a domeshapedseal. One of the cylinders is slightly longer but smaller in diameterthan the other and is termed the base or body. This member is filledwith the drug mixture or medicament or other substances and is thenforced into the other cylinder which is termed the cap. The capgenerally fits fairly tightly over the base, but even though the cap andbase are made with the greatest possible precision the assembled capsuleis usually not entirely spill-proof. The filled capsules will on roughhandling, for example, when passed through a high-speed machine forbranding or filling into bottles or other containers, show evidence ofspillage of the contentssometimes because of leakage between thesurfaces of the cap and the base, bht often because the cap and basecome apart. Accordingly, it is desirable that the hard gelatin capsuleafter filling be sealed so as to reduce leakage, to prevent the cap andbase from falling apart, and to reduce contamination of the contents byair, moisture, etc.

It is to be understood that the term sealing as employed in thespecification and claims includes not only treatments in which the gapbetween the cap and base of a capsule is completely closed but alsotreatments in which said gap is only partially closed. Sealing withinthe context of the present invention has been eiiected when the cap andbase cannot be separated or can be separated only with difficulty byhand.

A number of methods have been adopted in the past to eifect suchsealing. One such method consists in treating the cap, beforeapplication to the base, with hot water or aqueous alcohol on the insidesurface, and then placing the cap over the base. A weld-type of seal isthus effected between the outer surface of the base and the innersurface of the cap. However, this method is subject to a number ofdisadvantages. The capsules must be handled and treated individuallywhen applying this method and further the water or other solventemployed will come into contact with the contents of the base and inmany instances will have a deleterious effect thereon. The methodtherefore is of limited application where the contents of the capsuleare of an unstable nature, and is also not useful in the large-scaleproduction and mechanical handling of capsules. Furthermore, distortionand disfigurement of the capsules have also resulted from application ofthe above method.

Another method which has been employed to seal hard capsules comprisesthe dipping of the filled and assembled capsule in a solution of aqueousformaldehyde. This process, however, has a denaturing effect upon thegelatin which becomes more difficult to digest in the gastrointestinaltract. Hence, the method cannot be used to encapsulate medicaments whichare required to be released in the gastro-intestinal tract within arelatively short period of time. Further, the method results in smallamounts of formaldehyde solution entering the capsules, particularlywhere the cap does not fit tightly over the base. In the case of manyproteinaceous medicaments or other susceptible substances, it isundesirable to introduce formaldehyde to the contents of the capsule inthis way because of the possibility of adverse interactions and themethod has not been used with any great success.

A method of sealing which is commonly employed consists in placing aband of gelatin in a slightly molten state around the joint between thecap and the base. The use of this method, however, requires expensivemachinery, since each capsule must be banded individually. Further, themethod requires rigorous inspection of all banded capsules to reject anywhich have not been sealed satisfactorily. Accordingly, the use of themethod increases considerably the cost and the production time involvedin the sealing of the capsules. Another method proposed for the sealingof hard gelatin capsules involves heat treatment as set forth in US.Patent 2,738,827. This method produces distortion of the capsule andapplication of heat to the capsule cannot be carried out in the case ofcapsules containing heat-labile material.

We have now found that filled hard gelatin capsules can be sealed afterassembly in a simple and convenient manner which lends itself readily tolarge-scale operation at low cost. The process of the invention consistsin contacting a hard gelatin capsule, which has been filled withmedicament or other material and then fully assembled, with a sealingfluid comprising a dispersion of an airdrying, hydrophilic, film-formingpolymer in an organic solvent.

The organic solvents which can be employed in the process of theinvention include lower alkanols such as methanol, ethanol, propanol,isopropyl alcohol, and the like, lower alkanones such as acetone, methylethyl ketone, diethyl ketone, methyl isobutyl ketone and the like, andlower aliphatic chlorinated hydrocarbons such as trichloroethylene,carbon tetrachloride, dichlorethane, tetrachloroethane and the like, andmixtures of any of the above-named solvents. Where a lower alkanol isemployed as solvent it is advantageous that said alkanol should containa small amount of water. However the amount of water present in saidalkanol should not be substantially greater than about 5 percent byvolume otherwise distortion of the capsules may occur.

Air-drying, hydrophilic, film-forming polymers which can be used in theprocess of the invention include polycarboxylic acid polymers, i.e.,polymers which contain free carboxylic acid groups in the units formingthe polymer, and polyhydroxylated polymers, i.e., polymers which containfree hydroxyl groups in the units forming the polymer.

Examples of polycarboxylic acid polymers are hydrolyzed styrene-maleicanhydride copolymers, polyvinyl ether-maleic anhydride copolymers whichhave been hydrolyzed or alcoholized, and polyacrylic acids.

The hydrolyzed styrene-maleic anhydride copolymers which canbe used inthe process of the invention comprise styrene-maleic anhydridecopolymers which are more than 50 percent hydrolyzed. The copolymer canbe modified to a minor extent by the presence of some otherhomopolymer-izable ethylenic unit, such as that of acrylonitrile,acrylic acid, methacrylic acid, itaconic acid, vinyl chloride,vinylidene chloride, dipentene, and the like. As used in the presentspecification the term hydrolyzed styrene-maleic anhydride copolymerincludes such modifications as well as modifications in the structureand method of preparation which do not alter the essential resinousnature, toxicity and acid properties of the copolymer.

Essentially the styrene-maleic anhydride copolymers which can beemployed in the process of the present invention can be represented bythe following formula:

RX YD wherein R represents homopolymerizable ethylenic units of whichmore than 70 percent are styrene units (the other ethylenic units beingthose of acrylonitrile, acrylic acid, methacrylic acid, itaoonic acid,vinyl chloride, vinylidene chloride, dipentene, and the like), Xrepresents ethylenic units of maleic acid and maleic anhydride of whichmore than 50 percent are maleic acid units (preferably more than 70percent), and x/y equals from 1 to about 4 (preferably from 1 to about1.2). The average molecular weight of the copolymer ranges from about20,000 to about 200,000.

it is to be understood that, in its broader aspects, the presentinvention relates to hydrolyzed styrene-maleic anhydride copolymerswhich are more than 50 percent hydrolyzed. It includes the materialdescribed no matter how it is produced or how it is modified so long asthe structure of the copolymer is primarily that of hydrolyzedstyrene-maleic anhydride copolymer of the indicated properties andstructure.

Styrene-maleic anhydride copolymer is a commercially available compoundwhich can be obtained in modified or unmodified form. Resin SC-2 isavailable from the Monsanto Chemical Company and is a modifiedstyrenemaleic anhydride copolymer. These copolymers are hydrolyzed toobtain a styrene-maleic acid copolymer which is useful in the process ofthe present invention. The hydrolysis can be partial or it can becomplete and involves a conversion of the acid anhydride linkages toOc-dlCfllbDXYiiC acid units. It is preferred that the hydrolysis besubstantially complete i.e., more than about 50 percent complete.

Polyvinyl ether-maleic anhydride copolymers which can be used in theprocess of the invention, after hydrolysis or alcoholysis as hereinafterdescribed, are the linear copolymers of alternating methyl vinyl etherand maleic anhydride units. Examples of such copolymers are those whichare available commercially from the General Aniline and Film Corporationunder the designation PVM/MA. These copolymers can be obtained withdifferent viscosity ranges varying from 0.2 to 6 18p) (1 g./ 100 ml. of2-butanone at 25 C.) according to the chain length. These commerciallyavailable copolymers do not themselves contain hydrophilic groups butwhen dissolved in water or in alkanols are hydrolyzed or alcoholyzedwith the formation of free carboxylic acid groups. Thus when dissolvedin water the anhydride groups are hydrolyzed to m'aleic acid residues.When dissolved in alkanols the anhydride groups break down with theformation of half esters leaving one free carboxylic group in eachmaleic acid residue. Accordingly these copolymers are employed in theprocess of the invention in the form of a solution thereof preferably ina lower alkanol such as ethanol which solution may contain up to aboutpercent water as hereinbefore described. The copolymers can be dissolveddirectly in the alkanol but the rate of solution is slow and solutionsare prepared more conveniently by first dissolving the copolymer in asmall amount of a ketone such as acetone, methyl ethyl ketone, and thelike, and then diluting the resulting solution with the lower alkanol.

The polyacrylic acids which can be used in the process of the inventioninclude polyacrylic acid, polymethacrylic acid and partially orcompletely hydrolyzed polyacrylonitrile, polymethacrylonitrile,polyacrylamide, polymethacrylamide, polyacrylic acid esters,polymethacrylic acid esters and copolymers of acrylic acid ormethacrylic acid with acrylonitrile, acrylamide or acrylic acid esters.Advantageously the hydrolysis of the said nitriles, amides and estersand copolymers thereof is more than 50 percent complete and preferablythe hydrolysis is substantially 100 percent complete. It is to beunderstood that the term polyacrylic acids as used in the specificationand claims includes both polyacrylic acid and all the above-mentionedderivatives thereof. Typical polyacrylic acids are Acrysol A1 andAcrysol A-3, marketed by the Rohm and Haas Company. Typical ofcommercially available polyacrylamides is PAM 10 which is marketed byAmerican Cyanamid Company. This product has a molecular weight in therange of 38,000 to 48,500 and can be hydrolyzed by heating with theappropriate quantity of aqueous caustic soda to give polyacrylic acids,containing from to 90 percent amide groups, which can be used in theprocess of the invention.

Examples of polyhydroxylated polymers are polyvinylalcohols,polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, andpartially etherified cellulose.

The term polyvinylalcohols includes all polymers produced by thehydrolysis of polyvinyl esters, usually the acetate. The properties ofthese polymers vary according to the molecular weight of the parentpolyvinylacetate and the extent of hydrolysis. The degree of hydrolysisis generally indicated by the percent acetate content and for thepurposes of the present invention it is preferred to use polyvinylalcohols wherein the acetate content is within the range of aboutpercent to about 50 percent. The molecular Weight of polyvinyl alcoholvaries from about 10,000 to about 400,000 but, for the purposes of thepresent invention we prefer to use material having a molecular weightwithin the range of about 25,000 to about 50,000. Typical of productswhich are commercially available is Elvanol 72-60 Polyvinyl alcoholwhich is marketed by E. I. du Pont de Nemours and Company.

The term partially etherified celluloses includes the methyl, ethyl andhigher alkyl ethers of cellulose in which 1 name Ethocel is typical.

. N-vinylpyrrolidone.

not all the hydroxy groups are etherified. The preferred alkyl celluloseis ethyl cellulose in which the ethoxyl content ranges from about 43 toabout 50 percent, of which the product available commercially under theAdvantageously, the partially etherified celluloses are employed in theprocess of the invention in the form of solutions in chlorinatedhydrocarbon solvents such as those hereinbefore described.

Polyvinylpyrrolidone is a macromolecular polymer of It is availablecommercially in a variety of forms having molecular weights ranging from1 and PVP/VA E-535, in which the ratio of N-vinylpyrrolidone tovinylacetate is 70:30, 60:40, and 50:50, respectively, are marketed byAntara Chemicals as 50 percent solutions of the copolymers in anhydrousethanol.

The concentration of air-drying, hydrophilic, filmforming polymer,hereinafter referred to as filler material, present in the sealing fluidemployed in the process of the invention is advantageously within therange of about 1 percent to about 20 percent. The use of concentrationshigher than 20 percent leads to practical difliculties due to the highviscosity of the sealing fluid and to excessive deposit of fillermaterial on the treated capsules. Preferably the concentration of fillermaterial in the sealing fluid is within the range of about 2.5 to about5.0 percent.

The process of contacting the filled capsules with the sealing fluid canbe carried out in a number of ways. Thus the capsules can be dipped intothe sealing fluid using apparatus which is conventional for suchpurposes. Alternatively and preferably the capsules can be sprayed withthe sealing fluid using conventional apparatus. The actual time duringwhich the sealing fluid is in contact with the capsule is not critical,the essential requirement being that the area of the capsule around theregion of the joint between the cap and base be thoroughly wetted withthe sealing fluid. However, unduly prolonged contact between the sealingfluid and the capsules is to be avoided to minimize the possibility ofcontamination of the contents of the capsule. In general a contact timeof the order of about seconds or less is sufficient to effect excellentsealing of the capsules.

When the concentration of filler material in the sealing fluid is withinthe preferred range of about 2.5 to about 5 percent the amount of fillermaterial which remains on the external surface of the capsules, afterthe latter have been contacted with the sealing fluid and allowed todrain, is very small and no washing or other treatment of the capsulesis necessary before these are dried. However, when higher concentrationsof filler material are employed it is desirable to Wash the capsulesafter contacting the latter with sealing fluid to avoid the presence ofexcessive deposits of filler material on the capsules. The Washing canbe effected using the same solvent employed in the sealing fluid orusing any of the other solvents listed above. After washing, thecapsules are dried. The drying step can be accomplished using methodswell known in the art, for example by exposing the treated capsules to acurrent of dry air.

Generally speaking the amount of filler material which remains on thesurface of the capsule after sealing according to the process of theinvention is very small and is usually of the order of about 20milligrams to about 100 milligrams. The actual amount deposited on thecapsule naturally varies with the size of the capsule. The capsule ofsize 0, which is that most frequently used in dispensing pharmaceuticalpreparations, has been found to have about 30 to about 40 milligrams offiller material deposited on its surface (including the gap between theapposite sides of the cap and base) after sealing according to theprocess of the invention.

When the capsules, which are sealed according to the process of theinvention, are intended to be used for pharmaceutical purposes it isnecessary to employ a filler material which is pharmaceuticallyacceptable. The preferred filler materials for this purpose arepolyvinylpyrrolidone and hydrolyzed styrene-maleic anhydride copolymers.Where the sealed capsules are to be employed for non-pharmaceuticalpurposes, such considerations of purity of the filler material do notapply.

A particularly convenient method of carrying out the steps of sealingand, if desired, washing the capsules consists in supporting the filledcapsules, for example on a wire mesh screen, whilst moving the capsulessuccessively through an area in which they are sprayed with sealingfluid, then, if desired, through an area in which they are sprayed withwashing solvent, and finally through an area in which they are dried.

We have found that in certain instances capsules which have been sealedby the process of the invention do not pass smoothly through ahigh-speed filling machine used in packaging the sealed capsule inbottles and the like containers. We have found that this problem can beovercome readily by incorporating a surfactant into the sealing fluid.Only a small amount of surfactant is necessary in order to accomplishthe desired result. Advantageously, the amount of surfactant present inthe sealing fluid is of the order of about 0.05 to 0.5 percent andpreferably of the order of 0.1 percent.

Generally speaking any surfactant, which is soluble at theconcentrations given above in the organic solvents employed in theprocess of the invention, can be employed for the above purpose.Advantageously the surfactants employed in the sealing fluid arenonionic surfactants such as ethylene oxide-polypropylene glycolcondensates (Pluronic F68), sorbitan higher aliphatic acid esters (Span80, Span 85), polyoxyethylene sorbitan higher aliphatic esters (Tween20), nonylphenoxy polyoxyethylene ethanol (Igepal (IO-430), and thelike.

We have found that capsules which have been sealed according to theprocess of the invention show excellent handling and storage properties.Thus the capsules do not leak when subjected to the vigorous handlinginvolved in packaging and shipping. The contents of the capsules are notcontaminated in any Way during the sealing process and the process ofthe invention can be applied to the sealing of capsules containing aWide variety of materials. For example, capsules containing thefollowing medicaments can be sealed efliciently and permanently by theprocess of the invention: Panalba (a mixture of tetracycline phosphatewith novobiocin), novobiocin, Comycin (a mixture of tetracyclinephosphate with nystatin), Alba-Penicillin (a mixture of novobiocin andpenicillin). a mixture of methoxyphenamine and aminophylline, Polykol(an oxyethylene oxypropylene polymer) and Casakol (a mixture of Polykoland casanthranol).

Accordingly, the process of the invention is a significant step forwardin the art of hard capsule sealing. The process provides a method ofsealing capsules which is simple, effective, and economical to use onthe large scale. The process does not require individual handling ofcapsules, and can be employed on a large scale without the use ofexpensive machinery.

The following examples are illustrative of the process and products ofthe present invention but are not to be construed as l'nniting:

EXAMPLE 1 A batch of 100,000 hard filled gelatin capsules (size 0)containing lactose was sealed using the following procedure. The sealingfluid employed in the process had the following composition.

Percent by weight Polyvinylpyrrolidone (Plasdone) (molecular weight=ca.40,000) 2.5 Pluronic P68 0.1 Ethanol (S.D. 3A) 97.4

The capsules were fed continuously on to a stainless steel wire meshconveyor traveling at about 15 feet per minute. The capsules werecarried by the conveyor through an area in which they were sprayed withthe above sealing fluid. The spraying device was equipped with means forcollecting and recirculating the sealing fluid. After spraying withsealing fluid the capsules were fed into a rotating tube in which theywere tumbled and subjected to a blast of dry air. The time taken to passthrough this tube was 30 to 60 seconds. The capsules were allowed toair-dry for about 12 to 24 bonus. The dry, sealed capsules so producedwere then packaged using conventional procedures.

EXAMPLE 2 A batch of 100,000 hard filled gelatin capsules (size 0)containing lactose was sealed using the procedure described in Example 1but employing a sealing fluid having the following composition.

Percent by weight Hydrolyzed styrene-maleic anhydride copolymer(prepared as described in U.S. Patent 2,897,121, Table VI, PreparationH) 2.5 Ethanol (SD. 3A) 97.5

EXAMPLE 3 Hard filled capsules containing aspirin 'were sealed using theprocedure described in Example 1 but employ ing a sealing fluid havingthe following composition.

Percent by weight Polyvinylpyrrolidone (Plasdone) (molecular weight ca.40 ,000) 2.5 Pluronic F68 0.1 Absolute ethanol 97.4

EXAMPLE 4 Hard filled capsules containing lactose were sealed bysuspending the capsules in a Wire mesh basket and dipping said basketfor a period of approximately seconds in a sealing fluid having thefollowing composition.

Percent by weight Ethyl cellulose (Ethocel; centipoises) 2.5Trichloroethylene 97.5

After being dipped the capsules were allowed to drain and were thendried in a current of dry air.

EXAMPLE 5 The sealing fluid was prepared by dissolving the PVM/ MA inthe methyl ethyl ketone and diluting the resulting solution with thealcohol.

EXAMPLE 6 Using the procedure and the sealing fluid described in Example1, hard filled capsules containing the following medicaments weresealed:

Panalba (tetracycline+novobiocin) Albamycin (novobiocin) Comycin(tetracycline-l-nystatin) Alba-Penicillin (novobiocin-l-potassiumpenicillin G) Orthoxine (methoxyphenarnine+aminophylline) Some of thesealed capsules were maintained at 47 C. for 1 month and others weremaintained at 40 C. for 3 months. At the end of the storage period thecontents of the capsules were assayed and the assays were compared withthose of unsealed capsules maintained under the same storage conditions.The assay results are recorded in the following table from which it willbe seen that the sealed capsules exhibited the same storagecharacteristics as the unsealed capsules.

Table said capsule but insuflicient to deposit a significant amount ofcoating on the exposed surfaces of said capsule.

2. The process of claim 1 wherein the sealing fluid also contains anonionic surfactant.

3. A process for sealing a filled hard gelatin capsule which comprisescontacting said filled and fully assembled capsule with a sealing fluidcomprising a dispersion of an air-drying, hydrophilic, film-formingpolymer selected from the class consisting of polyvinylpyrrolidone andhydrolyzed styrene-maleic anhydride copolymer, in an organic solventselected from the class consisting of lower-allanols, lower-alkanones,and lower-aliphatic chlorinated hydrocarbons, said capsule beingcontacted with said sealing fluid for a time sufficient to wetthoroughly with sealing fluid the joint between the cap and the base ofsaid capsule but insuflicient to deposit a significant amount of coatingon the exposed surfaces of said capsule.

4. The process of claim 3 wherein the sealing fluid also contains anonionic surfactant.

5. A process for sealing a filled hard gelatin capsule which comprisescontacting said filled and fully assembled capsule with a sealing fluidcomprising a solution of polyvinylpyrrolidone in ethanol containing fromO to about 5 percent by volume of water said capsule being contactedwith said sealing fluid for a time sufficient to wet thoroughly withsealing fluid the joint between the cap and the base of said capsule butinsuflicient to deposit a significant amount of coating on the exposedsurfaces of said capsule.

6. The process of claim 5 in which the sealing fluid also contains anonionic surfactant.

7. The process of claim 5 in which the concentration ofpolyvinylpyrrolidone in the sealing fluid is from about 2.5 to about 5percent by weight.

3. A process for sealing a filled hard gelatin capsule which comprisescontacting said filled and fully assembled capsule with a sealing fluidcomprising a solution of a hydrolyzed styrene-maleic anhydride copolymerin ethanol containing from 0 to about 5 percent by volume of water saidcapsule being contacted with said sealing fluid for a time suflicient towet thoroughly with sealing STABILITY DATA ON HARD FILLED CAPSULESSEALED W ITI I POLYVINYLPYRROLIDONE All assays expressed in mg. unlessotherwise indicated Initial 1 Month 47 C. 3 Months 40 0.

Control PVP Sealed Control PVP Sealed Control PVP Sealed II. I 0.Panalba: F

Tetracycline Hydrochloride 263 263 258 203 259 2n Novobiocin 127. 5 128.129 132. 5 12:) 12a Moisture, percent..- 4, 05 4.16 H. F. C. Albamycin,250

N ovobiocin 250 253 255 250 242. 5 240 Moisture, percent. 3. 44. 3. 7311 F. 0. Com cin: n

Tetracycline Hydrochloride 275 272. 5 2 253 JO Nystatln, units 303, 000300, 000 261, 250 200, 250 247, 500 250, 000

Moisture, percent. 4. 6s 5. 27 H. F. O. Alba-Pcnicill Novobiocin 283. 8261. 3 262. 5 260 "5 256 Penicillin G Potassium, units 266, 000 270, 000269, 000 267, 000 266, 000 206, 000 H. F. C. Orthoxine and AminophylliAminophylliiie 103. 1 111. 2 99 100 101 102. 2

Orthoxine Hydrochloride 49. 7 49. 7 49. 9 50. 2 49. 1 i9. 7

We claim:

1. A process for sealing a filled hard gelatin capsule which comprisescontacting said filled and fully assembled capsule with a sealing fluidcomprising a dispersion of an air-drying, hydrophilic, film-formiugpolymer in an organic solvent selected from the class consisting ofloweralkanols, lower-alkanones, and lower-aliphatic chlorinatedhydrocarbons, said capsule being contacted with said sealing fluid for atime sufficient to wet thoroughly with sealing fluid the joint betweenthe cap and the base of fluid the joint between the cap and the base ofsaid capsule but insuflicient to deposit a significant amount of coatingon the exposed surfaces of said capsule.

9. The process of claim 8 in which the concentration 70 of hydrolyzedstyreiie-maleic anhydride copolymer in the Sealing fluid is from about2.5 to about 5 percent by weight.

10. A process for sealing a filled hard gelatin capsule which comprisesthe steps of contacting said filled and 5 fully assembled capsule with asealing fluid comprising 9 a dispersion of an air-drying, hydrophilic,film-forming polymer selected from the class consisting ofpolyvinylpyrrolidone and hydrolyzed styrene-maleic anhydride copolymerin an organic solvent, washing the sealed capsule with an organicsolvent, and drying the washed, sealed capsule.

11. The process of claim 10 in which the sealing fluid also contains anonionic surfactant.

12. A hard gelatin capsule having deposited thereon between the appositesurfaces of the cap and the base a film formed from an air-drying,hydrophilic, homogeneous film-forming polymer.

13. A hard gelatin capsule having deposited thereon between the appositesurfaces of the cap and the base a homogeneous film formed frompolyvinylpyrrolidone.

14. A hard gelatin capsule having deposited thereon between the appositesurfaces of the cap and the base a homogeneous film formed from ahydrolyzed styrenemaleic anhydride copolymer.

15. A hard gelatin capsule having deposited on the outer surfacethereof, including the apposite surfaces of the cap and the base, fromabout 20 milligrams to about 100 milligrams of a homogeneous film formedfrom an air-drying, hydrophilic, film-forming polymer.

16. A process for sealing a filled hard gelatin capsule which consistsin the steps or contacting said filled and fully assembled unsealedcapsule with a sealing fluid comprising a dispersion of an air-drying,hydrophilic, film-forming polymer in an organic solvent selected fromthe class consisting of lower alkanols, lower alkanones, andlower-aliphatic chlorinated hydrocarbons, removing comprises the stepsof contacting said filled and fully assembled unsealed capsule with asealing fluid comprising a solution of said polymer in an organicsolvent selected from the class consisting of lower alkanols,loweralkanones, and lower-aliphatic chlorinated hydrocarbons, removingsaid capsule from contact with said sealing fluid, and air-drying saidcapsule to form a non-sticky homogeneous film of said polymer betweenthe cap and the base of said capsule.

References Cited in the file of this patent UNITED STATES PATENTS2,897,121 Wagner l uly 28, 1959 2,924,920 Margolis Feb. 16, 1960 FOREIGNPATENTS 536,875 Canada Feb. 5, 1957 OTHER REFERENCES Drug & Cosmetic,July 1954, p. 36. The Art of Compounding, Ninth Edition, McGraw- Hill,New York, 1957, pp. 61, 77-79. (Copy in Div. 43.)

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent N0a3,071,513 January 1, 1963 Herman R, De Boer et all,

It is hereby certified that error appears in the above numbered patentrequiring correction and that the said Letters Patent should read ascorrected below.

Column 9, line 10, after "a" insert homogeneous line 11, strike out"homogeneous",

Signed and sealed this 16th day of July 1963 (SEAL) Attest:

ERNEST w. SWIDER DAVID LADD Attesting Officer 3 Commissioner of Patents

1. A PROCESS FOR SEALING A FILLED HARD GELATIN CAPSULE WHICH COMPRISESCONTACTING SAID FILLED AND FULLY ASSEMBLED CAPSULE WITH A SEALING FLUIDCOMPRISING A DISPERSION OF AN AIR-DRYING, HYDROPHILIC, FILM-FORMINGPOLYMER IN AN ORGANIC SOLVENT SELECTED FROM THE CLASS CONSISTING OFLOWERALKANOLS, LOWER-ALKANONES, AND LOWER-ALIPHATIC CHLORINATEDHYDROCARBONS, SAID CAPSULE BEING CONTACTED WITH SAID SEALING FLUID FORTIME SUFFICIENT TO WET THROUGHLY WITH SEALING FLUID THE JOINT BETWEENTHE CAP AND THE BASE OF SAID CAPSULE BUT INSUFFICIENT TO DEPOSIT ASIGNIFICANT AMOUNT OF COATING ON THE EXPOSED SURFACES OF SAID CAPSULE.